This invention relates to the detection of bacterial vaginosis using a gas detector.
Bacterial vaginosis (EV) is a well known, but not well understood or well defined, condition which exhibits uncertain symptoms. Numerous reports cite as much as 50% of the affected population being asymptomatic. The remaining 50% of the population either go undetected or present during routine examination for an associated or uncorrelated problem.
Originally thought to be a benign infection recent studies have linked the problem to increased risk of intra-amniotic infection, choroamionitis, post-caesarean and post-partum endometritis, adverse pregnancy outcome, pre-term labour and birth, premature rupture of membranes at term and post-hysterectomy cuff cellulitis.
BV is commonly thought to arise as a result of fluctuation of the normal vaginal flora, In some cases the flora can fluctuate naturally over the menstrual cycle with no adverse effects. It is thought that one of the primary controlling mechanisms controlling BV causative bacteria is the presence of adequate colonies of Lactobacillus sp. that produce hydrogen peroxide. The most common organisms associated with BV are: Gardnerella vaginalis, Bacteroides (Prevotella) spp., Mobiuncus spp. and Mycoplasma hominis. However, the presence or absence of these flora is not reliably diagnostic.
Treatment after a correct diagnosis is usually quite effective and usually comprises of treatment with oral doses of metronidazole. Topical treatments with metronidazole or clindamycin are also common. However, in Doctors' surgeries it is not uncommon for general practitioners (GPs) to wrongly diagnose vaginal infections, e.g., some cases of Candida are diagnosed as BV and vice versa. A distinction between a yeast and bacterial infection is important, as non-specific antibiotics can cause more problems for the sufferer. For symptomatic patients, BV has an incidence of 40% compared with Candida and Trichomonas. A swift, preferably in-situ, diagnosis would enable immediate correct therapy (usually comprising antibiotics in the case of DV) to be administered. In GPs' surgeres, a means of differentiating a bacterial infection from a yeast infection would enable the correct type of treatment to be prescribed.
In fact, the consequences of BV are wide and varied and are not completely understood. This is perhaps unsurprising given the difficulties in getting reliable BV data for a population. The primary challenge facing any prospective diagnostic technique (or aid to diagnosis) is finding a unique indicator against which BV may be detected. Currently the Amsel test is the benchmark for determining the problem. The criteria for the test rely on at least three out of four conditions being met. These are;                pH of vaginal fluid >4.5        Typical thin, homogenous vaginal discharge        Release of strong fishy smell on adding alkali (10% KOH) to a sample of vaginal fluid (whiff test),        Clue cells present on microscopic examination of a wet mount of vaginal fluid.        
It should be noted that the presence of trimethylamine (TMA) in some BV samples is undisputed, and TMA is often cited as being the volatile associated with the unpleasant fishy odour referred to above.
Individually none of these tests are diagnostic. pH variation of the vaginal fluid is nearly always present in BV positive patients but it is a non-specific. test and the variation is equally likely to be caused by another infection or problem. Additionally, contamination of the sample by cervical mucus (typical pH 7) can lead to false diagnoses in some cases. pH variation also occurs as part of the natural menstrual cycle. Ethnic background is also a factor affecting vaginal pH and his has been postulated as a reason for the relatively higher number of black American women who present with the disease. According to Hay, pH is highly sensitive (97%) but very non-specific giving false positives in 47% of cases. Conversely, discharge is very accurately recognised by clinicians giving false positives at 3% but only has a specificity of 67%. Following this, the “whiff” test also gives low false positives (1%) but is non-specific (43%). Finally clue cells are typically found in 81% of positive BV cases whilst 6% of non-BV cases have positive clue cell tests. Other trials report variation on these figures but all concur with the non-specificity and reliability of any one individual test.
It is known from the applicant's International Application No. WO 95/33848 that microorganisms can be detected using arrays of gas sensors to detect characteristic gases or vapours produced by the microorganisms. An example of such an array is an array of semiconducting organic polymer gas sensors. The applicant's International Applications Nos. WO 98/29563 and WO 98/39470 describe further aspects and refinements to the technique, and related developments. In general, the approach with arrays of gas sensors is to utilise a large number (twenty, thirty or more) of different gas sensors which possesses different but overlapping sensitivities towards different gaseous species (so-called “electronic noses”). Oases are recognised from the characteristic “fingerprint” or pattern of response across the array. However, detection can be difficult in a complex system having mixed populations of microflora and microfaunae and/or systems in which many volatile species are present.
Of the particular relevance to the present application are International Application number WO 94/04916 and Chandiok et al (S. Chandiok, B A Crawley, B A Oppenhein, P R Chadwick, S Higgins, and K C Persaud, Journal of Clinical Pathology, 50 (1997) 790). Both documents describe attempts to detect BV using arrays of semiconducting organic polymers, and in both cases it is believed that the gaseous species detected were ammonia and/or TMA. In fact, WO 94/04916 specifically describes a process rather similar to the whiff test discussed above, in which KOH is added to a sample, thereby releasing volatile alkaline species into the gas phase. It should be noted, when considering the present invention as described below, that the sensors used in the investigation of Chandiok et al are not sensitive to fatty acids such as acetic acid.